Engineering Chirally Blind Protein Pseudocapsids into Antibacterial Persisters.
ACS Nano
; 14(2): 1609-1622, 2020 02 25.
Article
in En
| MEDLINE
| ID: mdl-31794180
Antimicrobial resistance stimulates the search for antimicrobial forms that may be less subject to acquired resistance. Here we report a conceptual design of protein pseudocapsids exhibiting a broad spectrum of antimicrobial activities. Unlike conventional antibiotics, these agents are effective against phenotypic bacterial variants, while clearing "superbugs" in vivo without toxicity. The design adopts an icosahedral architecture that is polymorphic in size, but not in shape, and that is available in both l and d epimeric forms. Using a combination of nanoscale and single-cell imaging we demonstrate that such pseudocapsids inflict rapid and irreparable damage to bacterial cells. In phospholipid membranes they rapidly convert into nanopores, which remain confined to the binding positions of individual pseudocapsids. This mechanism ensures precisely delivered influxes of high antimicrobial doses, rendering the design a versatile platform for engineering structurally diverse and functionally persistent antimicrobial agents.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Engineering
/
Escherichia coli
/
Anti-Bacterial Agents
Type of study:
Clinical_trials
Language:
En
Journal:
ACS Nano
Year:
2020
Document type:
Article
Country of publication:
Estados Unidos